Prognostic Impact of Familial Screening in Dilated Cardiomyopathy
Prognostic Impact of Familial Screening in Dilated Cardiomyopathy
Aims Familial screening of patients with dilated cardiomyopathy (DCM) allows an early diagnosis of the disease in family members. It is unclear if familial forms (FDC) have a different long-term outcome compared with sporadic DCM. Our aim was to compare the long-term prognosis of FDC and sporadic forms in order to assess the role of familial screening.
Methods and results Between 1988 and 2007, 637 DCM patients were consecutively enrolled. Of these, 130 patients (20.4%) had FDC, including 82 (12.9%) probands and 48 (7.5%) non-proband FDC patients (NP-FDC), identified by family screening. We compared the 48 NP-FDC patients with a sample of 96 patients with sporadic DCM, who were randomly matched by year of enrolment in a 2:1 ratio. At enrolment the NP-FDC patients were younger (40 ± 16 vs. 48 ± 13 years, P = 0.002), less symptomatic [New York Heart Association, (NYHA) III–IV: 8 vs. 28%, P = 0.006], had higher left ventricular ejection fraction (35 ± 10 vs. 30 ± 9%, P = 0.005) and were less intensively treated with evidence-based drugs than the sporadic DCM patients. Survival free from heart transplant at 2, 5 and 10 years was 93, 91 and 82%, respectively, in NP-FDC patients compared with 86, 76 and 62% in sporadic forms (P = 0.04). After stratification for NYHA classes, no difference in survival was observed between sporadic and NP-FDC patients.
Conclusion Our study demonstrates that family screening can effectively identify DCM patients at an earlier stage of disease and can improve survival. The possibility of changing the prognosis of DCM needs to be verified in patients intensively treated with tailored medical treatment. Family screening should be recommended for all DCM patients.
Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by left ventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause the observed impairment. It is an important factor in mortality and morbidity, as well as a frequent indication for heart transplant.
An early diagnosis, at a less advanced disease stage, and the use of effective and evidence-based pharmacological treatment such as ACE inhibitors and beta-blockers, and non-pharmacological therapies such as an implantable cardioverter defibrillators (ICDs) and cardiac resynchronization, have contributed to the improved prognosis of DCM.
Dilated cardiomyopathy is defined as idiopathic, when the disease is sporadic, isolated in a single member of a family and without a known cause, or familial (FDC), when occurring in two or more related family members or in the presence of a relative with an unexpected sudden death before the age of 35.
The prevalence of FDC has been previously estimated at between 20 and 50%. FDC presents incomplete penetrance, variable expression, significant locus and allelic heterogeneity. Several gene defects that cause dilated cardiomyopathy have been identified, although these account for only a small proportion of cases.
In most follow-up studies of DCM, the study populations were not divided into familial and non-familial categories. In part, this is because there are no reliable clinical or morphologic parameters that are able to predict and differentiate the familial forms from non-genetic causes of cardiac dilatation. Thus it remains controversial whether the progression of disease differs in patients with FDC and sporadic DCM.
An accurate clinical-instrumental assessment of first-degree relatives appears to have fundamental relevance in the diagnosis of FDC for early recognition of asymptomatic affected relatives. Nevertheless, this approach is not yet widely practiced and there is currently no data available on its actual clinical benefit.
In this study we retrospectively analysed the DCM population enrolled in the Trieste Heart Muscle Disease Registry and assessed the long-term prognosis of FDC. In particular, we compared non-proband FDC patients (NP-FDC), with respect to sporadic non-familial forms of the disease, in order to assess the prognostic role of familial screening in a large cohort of DCM patients.
Abstract and Introduction
Abstract
Aims Familial screening of patients with dilated cardiomyopathy (DCM) allows an early diagnosis of the disease in family members. It is unclear if familial forms (FDC) have a different long-term outcome compared with sporadic DCM. Our aim was to compare the long-term prognosis of FDC and sporadic forms in order to assess the role of familial screening.
Methods and results Between 1988 and 2007, 637 DCM patients were consecutively enrolled. Of these, 130 patients (20.4%) had FDC, including 82 (12.9%) probands and 48 (7.5%) non-proband FDC patients (NP-FDC), identified by family screening. We compared the 48 NP-FDC patients with a sample of 96 patients with sporadic DCM, who were randomly matched by year of enrolment in a 2:1 ratio. At enrolment the NP-FDC patients were younger (40 ± 16 vs. 48 ± 13 years, P = 0.002), less symptomatic [New York Heart Association, (NYHA) III–IV: 8 vs. 28%, P = 0.006], had higher left ventricular ejection fraction (35 ± 10 vs. 30 ± 9%, P = 0.005) and were less intensively treated with evidence-based drugs than the sporadic DCM patients. Survival free from heart transplant at 2, 5 and 10 years was 93, 91 and 82%, respectively, in NP-FDC patients compared with 86, 76 and 62% in sporadic forms (P = 0.04). After stratification for NYHA classes, no difference in survival was observed between sporadic and NP-FDC patients.
Conclusion Our study demonstrates that family screening can effectively identify DCM patients at an earlier stage of disease and can improve survival. The possibility of changing the prognosis of DCM needs to be verified in patients intensively treated with tailored medical treatment. Family screening should be recommended for all DCM patients.
Introduction
Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by left ventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause the observed impairment. It is an important factor in mortality and morbidity, as well as a frequent indication for heart transplant.
An early diagnosis, at a less advanced disease stage, and the use of effective and evidence-based pharmacological treatment such as ACE inhibitors and beta-blockers, and non-pharmacological therapies such as an implantable cardioverter defibrillators (ICDs) and cardiac resynchronization, have contributed to the improved prognosis of DCM.
Dilated cardiomyopathy is defined as idiopathic, when the disease is sporadic, isolated in a single member of a family and without a known cause, or familial (FDC), when occurring in two or more related family members or in the presence of a relative with an unexpected sudden death before the age of 35.
The prevalence of FDC has been previously estimated at between 20 and 50%. FDC presents incomplete penetrance, variable expression, significant locus and allelic heterogeneity. Several gene defects that cause dilated cardiomyopathy have been identified, although these account for only a small proportion of cases.
In most follow-up studies of DCM, the study populations were not divided into familial and non-familial categories. In part, this is because there are no reliable clinical or morphologic parameters that are able to predict and differentiate the familial forms from non-genetic causes of cardiac dilatation. Thus it remains controversial whether the progression of disease differs in patients with FDC and sporadic DCM.
An accurate clinical-instrumental assessment of first-degree relatives appears to have fundamental relevance in the diagnosis of FDC for early recognition of asymptomatic affected relatives. Nevertheless, this approach is not yet widely practiced and there is currently no data available on its actual clinical benefit.
In this study we retrospectively analysed the DCM population enrolled in the Trieste Heart Muscle Disease Registry and assessed the long-term prognosis of FDC. In particular, we compared non-proband FDC patients (NP-FDC), with respect to sporadic non-familial forms of the disease, in order to assess the prognostic role of familial screening in a large cohort of DCM patients.